High-temperature short-time treatment device, system, and method

ABSTRACT

A dual path heat exchanger integrated as a single unit able to process fluid stream through a continuous, single-use high temperature short time process. The heat exchanger contains both a heating section and a cooling section in the same unit. In one embodiment, the heating and cooling sections (which may be formed separately for other uses) are formed as a plate and frame structure with a thermally conductive thin film or foil forming the physical barrier between the process stream flow path and the thermal medium (heating or cooling) flow path. The film/foil renders the heat exchanger suitable for single-use and/or to be disposable. A manifold, which also may be formed as a single unit, may be used to transfer fluid flow between the sections of the heat exchanger, and/or to transfer fluid into and out of the system formed by the heat exchanger and manifold.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. § 119 to U.S. Provisional Application Ser. No. 63/057,020, filed Jul. 27, 2020, the disclosure of which is hereby incorporated herein by reference in its entirety for all purposes.

FIELD

The present disclosure relates generally to the field of sterilization and/or viral inactivation devices, systems, and methods. In particular, the present disclosure relates to high-temperature short-term (HTST) treatment devices, systems, and methods, such as for viral inactivation.

BACKGROUND

The use of heat for various sterilization processes has long been known in the art for various applications, such as pasteurization and viral inactivation. Heat exchangers are devices that allow heat from a hot fluid to pass to a second fluid without the two fluids having to mix together or come into direct contact. The principle of a heat exchanger relies on two fluid streams isolated from each other using a thermally conductive barrier therebetween. The thermally conductive barrier allows heat to be transferred from the hot fluid to the second fluid to be heated.

Heat inactivation, and, particularly, high-temperature short-time (HTST) treatment, which may utilize heat exchangers, has been evaluated by various biologics manufacturers as a potential upstream barrier technology for mitigating the risk of introducing adventitious viral contaminants into biological process streams. More particularly, HTST treatment has been evaluated for use in mitigating the risk of introducing adventitious viral contaminants into manufacturing processes via contaminated cell-culture reagents and other process solutions. Such treatment is generally considered to represent an efficacious and robust risk mitigation step for the inactivation of virus.

HTST treatment has additional commercial benefits in that it is generally a continuous process. As such, HTST treatment may be integrated into another continuous process such that a continuous purification process, which is particularly advantageous in a commercial setting, is easily accomplished.

More recently, single-use technologies, such as bioreactors for cell culture, tangential-flow filtration (TFF) systems for harvest, and other disposable technology options for many types of processing, such as in the biopharmaceutical industry, are being adopted. It may be desirable or advantageous to include HTST treatment with such processing. However, traditional heat exchangers are not ideally suited for a single-use continuous viral inactivation step. Without a viable high capacity single-use heat exchanger, process engineers have been forced to choose one of two options which are currently considered less than ideal. The first option is to insert a stainless-steel multiuse heat exchanger into the process. Typically, two discrete conventional heat exchangers constructed of stainless steel are used for HTST treatment, which would not address single-use applications desirable in the biopharmaceutical market. This option sacrifices the benefits of a full single-use set up, resulting in prolonged downtime (such as to sterilize the heat exchanger between processes), and expensive capital equipment. The second option is to use a jacketed mixing tote in place of a heat exchanger. The sacrifice accompanying this option is in terms of rate of heat transfer—jacketed mixing totes have not been designed for rapid temperature control. As such, neither of these solutions is ideal for a single use HTST application. Each has brought a series of problems for which the industry has had to contend with.

In view of the above, an economical HTST treatment device, system, and method would be welcome in the industry. In addition or alternatively, an HTST treatment device, system, and method configured and designed to be disposable and/or for single-use (such terms may be used interchangeably herein without intent to limit) applications, such as in the biopharmaceutical industry, would be welcome in the industry. In addition or alternatively, an HTST treatment device, system, and method which may be readily integrated into a continuous manufacturing process requiring heat inactivation at at least one stage of the process would be welcome in the industry.

SUMMARY

In one aspect, the present subject matter is directed to a heat exchanger having a heating section defining flow paths for heating medium along flow paths for a process stream, and a cooling section thermally and physically isolated from said heating section and defining flow paths for cooling medium along flow paths for a process stream. The heating medium flow paths are physically isolated from and thermally coupled with the process stream flow paths, and, similarly, the cooling medium flow paths are physically isolated from and thermally coupled with the process stream flow paths. The heat exchanger, as a single unit, includes process stream ports, heating medium ports, and cooling medium ports.

In some embodiments, a manifold is coupled to the heat exchanger, the manifold comprising, as a unit, manifold process stream ports corresponding to and in fluid communication with the heat exchanger process stream ports, manifold heating medium ports corresponding to and in fluid communication with the heat exchanger heating medium ports, and manifold cooling medium ports corresponding to and in fluid communication with the heat exchanger cooling medium ports, such that a process stream flows continuously through the heating section to the cooling section through the manifold.

In some embodiments, the manifold receives the process stream that has been heated through the heating section of the heat exchanger, transfers the heated process stream to the cooling section of the heat exchanger, and receives the process stream that has cooled through the cooling section of the heat exchanger.

In some embodiments, the heat exchanger of is a single unit and the manifold is a single unit mating with the heat exchanger single unit.

In some embodiments, the heat exchanger further comprises a plurality of stacked channel spacers defining the flow paths through the heat exchanger. In some further embodiments, the plurality of channel spacers seal fluid within the heat exchanger and isolate flow paths within the heat exchanger. In some further embodiments, each channel spacer defines the flow paths in the heating section and the cooling section of the heat exchanger. In some further embodiments, each channel spacer comprises a frame element and a flow element, wherein frame elements of stacked channel spacers are bonded together to form a peripheral seal about the heat exchanger as a unit and an insulative wall between the heating section and the cooling section within the heat exchanger.

In one aspect, the present subject matter is directed to a heat exchanger configured to be a single-use and/or disposable unit, with a plurality of channel spacers stacked together, each channel spacer defining a fluid flow channel for a fluid medium to flow therethrough; and a thermally conductive physical barrier, in the form of thin foil or film, sandwiched between adjacent channel spacers to conduct thermal energy between fluid mediums in adjacent channel spacers while physically isolating the fluid mediums from each other.

In some embodiments, the thermally conductive physical barrier is sufficiently thin to allow at least ten thermally conductive physical barrier in said heat exchanger without impeding on unassisted manual portability of said heat exchanger (a greater number of thermally conductive physical barriers than could normally be provided in a prior art heat exchanger not designed for single-use or to be disposed of or discarded). Each thermally conductive physical barrier may, in some embodiments, be no greater than 0.010″ (0.254 mm) thick. In some embodiments, each thermally conductive physical barrier is in the form of a thin foil or film that cannot maintain structural rigidity and shape unassisted. In some further embodiments, the channel spacers provide structural rigidity to the thermally conductive physical barriers.

In some embodiments, each channel spacer comprises a frame element and a screen element. In some further embodiments, each channel spacer further comprises a seal element sealing fluid flow between the frame element of the channel spacer, an upper thermally conductive physical barrier on one side of the channel spacer, and a lower thermally conductive physical barrier on an opposite side of the channel spacer.

In accordance with additional aspects of the present disclosure, the present subject matter is directed to a method of heating and cooling a process stream through a single heat exchanger unit along a continuous flow path using a thermal medium comprising a heating medium or a cooling medium. In accordance with some aspects, the method comprises providing a at least one process stream heating medium flow path and at least one heating medium flow path through a heating section of the single heat exchanger, the heating medium flow path extending along a process stream heating flow path to heat the process stream, and providing a at least one process stream cooling flow path and at least one cooling medium flow path through a cooling section of the single heat exchanger, the cooling medium flow path extending along a process stream cooling flow path to cool the process stream, wherein heating and cooling of a process stream is achieved in the same single heat exchanger.

In some embodiments, the method further comprises providing a plurality of system ports in the single heat exchanger, the system ports including process stream ports in fluid communication with the process stream flow paths through the single heat exchanger, and thermal medium ports in fluid communication with heating medium flow paths and cooling medium flow paths in the single heat exchanger.

In some embodiments, the method further comprises coupling the single heat exchanger with a mating manifold configured to distribute flow to the system ports in the single heat exchanger. In some embodiments, the manifold is provided with inlet and outlet ports for passage of process stream, a heating medium, and a cooling medium into or out of the manifold and thus the single heat exchanger.

In some embodiments, the method further comprises coupling the single heat exchanger to a mating manifold, the manifold transferring the process stream from the heating section to the cooling section of the single heat exchanger.

These and other features and advantages of the present disclosure will be readily apparent from the following detailed description, the scope of the claimed invention being set out in the appended claims.

This summary of the disclosure is given to aid understanding, and one of skill in the art will understand that each of the various aspects and features of the disclosure may advantageously be used separately in some instances, or in combination with other aspects and features of the disclosure in other instances. No limitation as to the scope of the claimed subject matter is intended by either the inclusion or non-inclusion of elements, components, or the like in this summary. Accordingly, while the disclosure is presented in terms of aspects or embodiments, it should be appreciated that individual aspects can be claimed separately or in combination with aspects and features of that embodiment or any other embodiment.

BRIEF DESCRIPTION OF THE DRAWINGS

The detailed description will be better understood in conjunction with the accompanying drawings, wherein like reference characters represent like elements, as follows:

FIG. 1 illustrates a perspective view of an example of a heat exchanger in accordance with various principles of the present disclosure.

FIG. 2 illustrates a cut-away view of the interior components of the heat exchanger of FIG. 1 and flow distribution manifold.

FIG. 3 illustrates a plan view of a process stream channel spacer which may be used in the heat exchanger of FIGS. 1 and 2.

FIG. 4 illustrates a plan view of a thermal medium channel spacer which may be used in the heat exchanger of FIGS. 1 and 2.

FIG. 5 illustrates a perspective view of an example of an HTST system in accordance with principles of the present disclosure.

FIG. 6 illustrates an exploded view of the HTST system of FIG. 5.

FIG. 7 illustrates a perspective view of an example of a manifold usable in the HTST system of FIGS. 5 and 6.

Non-limiting embodiments of the present disclosure are described by way of example with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. The accompanying drawings are provided for purposes of illustration only, and the dimensions, positions, order, and relative sizes reflected in the figures in the drawings may vary. In the figures, identical or nearly identical or equivalent elements are typically represented by the same reference characters. For purposes of clarity and simplicity, not every element is labeled in every figure, nor is every element of each embodiment shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure.

DETAILED DESCRIPTION

The following detailed description should be read with reference to the drawings, which, as noted above, depict illustrative embodiments. It will be appreciated that the present disclosure is set forth in various levels of detail in this application. In certain instances, details that are not necessary for one of ordinary skill in the art to understand the disclosure, or that render other details difficult to perceive may have been omitted. All of the devices and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. It should be understood that the claimed subject matter is not necessarily limited to the particular embodiments or arrangements described or illustrated herein, the scope of the claimed invention being set out in the appended claims.

Various embodiments of an HTST treatment device, system, and method will now be described. Reference in this specification to “one embodiment,” “an embodiment,” “some embodiments”, “other embodiments”, etc. indicates that one or more particular features, structures, and/or characteristics in accordance with principles of the present disclosure may be included in connection with the embodiment. However, such references do not necessarily mean that all embodiments include the particular features, structures, and/or characteristics, or that an embodiment includes all features, structures, and/or characteristics. Some embodiments may include one or more such features, structures, and/or characteristics, in various combinations thereof. Moreover, references to “one embodiment,” “an embodiment,” “some embodiments”, “other embodiments”, etc. in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments necessarily mutually exclusive of other embodiments. When particular features, structures, and/or characteristics are described in connection with one embodiment or component, it should be understood that such features, structures, and/or characteristics may also be used in connection with other embodiments or components whether or not explicitly described, unless clearly stated to the contrary. It should further be understood that such features, structures, and/or characteristics may be used or present in various combinations with one another to create alternative embodiments which are considered part of the present disclosure, as it would be too cumbersome to describe all of the numerous possible combinations and subcombinations of features, structures, and/or characteristics. Moreover, various features, structures, and/or characteristics are described which may be exhibited by some embodiments and not by others. Similarly, various features, structures, and/or characteristics or requirements are described which may be features, structures, and/or characteristics or requirements for some embodiments but may not be features, structures, and/or characteristics or requirements for other embodiments.

In accordance with various principles of the present disclosure, a device, system, and method for HTST treatment, such as for viral inactivation, may provide one or more benefits including cost-effectiveness; capability of continuous processing/being integrated into a continuous process; single-use configuration; and/or disposable configuration. The present disclosure provides, at least in some embodiments, a cost effective, single-use HTST device and process useful in achieving continuous HTST viral inactivation in a biopharmaceutical process. Sterilization or viral inactivation performed in accordance with or with devices or systems of the present disclosure may be particularly useful in biopharmaceutical processes in which retrieval of a process stream (e.g., stream of fluid in an overall process such as a purification train, including, inter alia, centrifuge, filter, chromatography, column, and other process, without limitation) in a short amount of time is desired. The device, system, and process disclosed herein utilizes a unique heat exchanger. Optionally, the device, system, and process disclosed herein utilizes a unique manifold in conjunction with the heat exchanger. It will be appreciated that principles applied to the heat exchanger and manifold components of the system described herein may be applied independently to heat exchangers and/or manifolds whether or not used in conjunction with an HTST process.

The principle of a heat exchanger relies on two fluid streams isolated from each other by a thermally conductive physical barrier. The barrier allows thermal energy to be transferred between the fluid streams. In accordance with one aspect of the present disclosure, the process stream is rapidly heated and then rapidly cooled to inactivate viral components or other pathogens or contaminants therein. Such heating and cooling, in accordance with one aspect of the present disclosure, takes place in a single heat exchanger or cassette housing a heating section as well as a cooling section. In a separate and independent aspect of the present disclosure, which may be independent from or in conjunction with the aforementioned aspect, such heating and cooling is a continuous process. For instance, flow into the device is equal to the flow out of the device, and the fluid flow does not have to stop or pause within a given processing device. In yet another separate and independent aspect of the present disclosure, which may be independent from or in conjunction with either of the aforementioned aspects, heating and cooling of a process stream is performed along a single flow path for the process stream, such flow path optionally being a continuous single flow path. In yet another separate and independent aspect of the present disclosure, which may be independent from or in conjunction with any of the aforementioned aspects, such heating and cooling is performed in a device configured and formed for a single use and/or to be disposable.

In accordance with one aspect of the present disclosure, a dual path heat exchanger is integrated into a single unit capable of processing a fluid stream starting at a temperature of as low as about 4° C. and as high as about 25° C. The heat exchanger is connected to a heat pump and a chiller which separately pass a thermal medium (e.g., glycol) into the heat exchanger in flow paths which are physically isolated from yet in thermal communication with the process stream flow path. More specifically, a hot medium (heated by an associated heating system) is passed through a heating section of the heat exchanger, and a cold medium (cooled by an associated cooling system) is passed through a cooling section of the heat exchanger. The medium to be processed by the heat exchanger (hereinafter, the “process stream” for the sake of simplicity and without intent to limit), such as a biological process stream, enters the heat exchanger via an inlet port and flows along a process stream heating flow path (optionally referenced as a “heated” or “hot” process stream flow path without intent to limit) through the heating section of the heat exchanger. The process stream and the hot medium (optionally referenced herein as “heating” or “heated” medium without intent to limit) are in thermal communication (and preferably physically/fluidly isolated) so that the process stream is rapidly heated to the desired temperature (e.g., approximately 70° C.-85° C. for typical applications). The process stream is held for a short period of time at an elevated temperature (e.g., over about 10 seconds) as it flows through the manifold from one side to the other. This hold time generally is determined by the flow rate and the size of the bore in the manifold. Thermocouples or temperature probes may be placed in the manifold to monitor the internal temperatures. The process stream then enters a cooling section (preferably thermally isolated from the heating path) in the heat exchanger and flows along a process stream cooling flow path (optionally referenced as a “cooled” or “cold” process stream flow path without intent to limit). The process stream and the cold medium (optionally referenced herein as “cooling” or “cooled” medium without intent to limit) are in thermal communication (and preferably physically/fluidly isolated) so that the process stream is rapidly cooled to the desired temperature (e.g., the initial starting temperature). In some embodiments, the heat exchanger flow paths includes one or more of the following components: a channel for fluid flow (for at least one of the process stream, the hot medium, or the cold medium); a turbulence promoter; and a thermally conductive material.

In some embodiments, the fluid flows are substantially planar (such as in a plate and frame heat exchanger) and separated by a thermally conductive physical barrier. In some embodiments, the barrier is in the form of a thin material, such as a polymeric film or foil, so that the heat exchanger is more amenable for ready disposal (is commonly considered disposable and for single use applications) in contrast with larger or heavier equipment with thicker walls (e.g., stainless steel walls as commonly used in prior art heat exchangers). Such single-use design/construction reduces the risk of cross-contamination from batch to batch, and thus is considered safer than prior art techniques, and particularly beneficial for drug manufacturing applications. A single-use heat exchanger is generally considered to be “ready to process” technology. For instance, because a single-use heat exchanger is not reused, it may be initially sterile and ready for use (unlike traditional heat exchangers which need to be autoclaved or otherwise sterilized). Moreover, a single-use, continuous process allows implementation of HTST viral inactivation not heretofore achievable with existing heat exchangers.

In accordance with some aspects of the present disclosure, the heating and cooling paths are in the same heat exchanger unit, simplifying the application over prior art heat exchangers which typically are constructed with a single path of the same thermal nature (either a single heating path or a single cooling path) and thus would require two separate units coupled together to provide the desired heating and cooling. In particular, a single heat exchanger unit containing both a heating path or section and a cooling path or section, as disclosed herein, is better adapted for HTST use than conventional heat exchangers, such as by providing heating and cooling in the same unit, and simplified construction and configuration over a more complex construction typically resulting from use of separate units for heating and cooling. In addition, provision of the heating path and cooling path in the same heat exchanger unit permits a single continuous flow path for the process stream. The process stream flows continuously from a heating section to a cooling section, and the flow is not interrupted by transport or waiting times in separate heating equipment and cooling equipment. In some embodiments, discussed in greater detail below, the process stream may flow through a manifold between the heating section and the cooling section of the heat exchanger, allowing the process stream to maintain an elevated temperature and flow continuously between the heating section and the cooling section.

In some embodiments, the heating path and the cooling path are substantially parallel to each other. In some embodiments, the flow direction of the process stream through the heating path is opposite the flow direction of the process stream through the cooling path. Such arrangement may allow for a more compact design. In some embodiments, independent of the relative positioning of the heating path and cooling path, the flow direction of the process stream is opposite the flow direction of the associated/adjacent thermal medium (the heating medium or the cooling medium). Such arrangement and counter current flow may allow for more efficient and maximized thermal transfer.

A heat exchanger system in accordance with the present disclosure may include a heat exchanger configured similar to a plate and frame heat exchanger, used in combination with a manifold, with clamping plates holding together the heat exchanger and manifold. The manifold may be a flow distribution manifold configured to direct the various fluid medium flows through the fluid paths of the heat exchanger. System ports (for flow of fluid within the system, and, in some embodiments facing the heat exchanger) in the manifold are in fluid communication with corresponding ports in the heat exchanger to allow the process stream and the thermal mediums (hot medium and cold medium) to flow from/to the respective heating and cooling sections of the heat exchanger, and be respectively distributed/collected by the manifold (e.g., distributed to the heating section; collected from the heating section; held in the transfer section; distributed to the cooling section; collected from the cooling section; etc.). Auxiliary ports in the manifold (e.g., on the side/periphery of the manifold) are provided for flow of medium into and out of the system (e.g., flow of process stream into or out of the heat exchanger from a source external to the manifold; or flow of thermal medium, heated or cooled by separate equipment, into the manifold for distribution to one of the heating or cooling sections of the heat exchanger; or flow of thermal medium away from the heat exchanger for reheating or recooling; etc.). As noted above, thermocouples or temperature probes may be used to monitor temperatures within the device to confirm the temperature requirements are met. In some embodiments, the manifold is manufactured from a single piece such as machined or molded plastic. As a single unit coupled to a single heat exchanger containing both a heating section and a cooling section, the manifold further contributes to the simplified design of the present disclosure, and the ability to provide a commercially viable continuous process for viral inactivation, such as via HTST treatment. The single unit also affords a cost savings over stainless steel and/or connecting two separate heat exchangers together.

Referring now to the drawings, an example of a heat exchanger 100 formed in accordance with principles of the present disclosure is shown in FIG. 1. Heat exchanger 100 has a heating section 110 and a cooling section 120. In the illustrated embodiment, the heating section 110 and cooling section 120 are bound by a common peripheral seal 102 or other common housing component forming a single-unit heat exchanger device which both heats and cools a process stream flowing therethrough. The heating section 110 and the cooling section 120 are thermally isolated from each other, such as by being separated by a thermal barrier, such as an insulative wall 104, to maximize or optimize heat exchange functions of each. The heating section 110 and the cooling section 120 are formed_side-by-side in the illustrated embodiment. However, other arrangements are within the scope of the present disclosure. Moreover, it will be appreciated that although heat exchanger 100 is illustrated as having a substantially cuboid shape, other configurations are within the scope of the present disclosure.

An example of a fluid flow pattern of the process stream and thermal mediums flowing through a heat exchanger 100 as shown in FIG. 1 is illustrated in FIG. 2, which is a cut-away view of the interior components of the heat exchanger 100 of FIG. 1 (juxtaposed with an example of a manifold described in further detail below with reference to FIGS. 5-7) schematically showing fluid flow therethrough. The process stream flows along a process stream flow path PFP within the heat exchanger 100. In one embodiment, the process stream flow path PFP is a substantially continuous flow path, such that the process stream flows uninterrupted through the heat exchanger 100. More particularly, the process stream flow path PFP may be an uninterrupted flow path. Even more particularly, the process stream flow path PFP may be continuous through both the heating section 110 and the cooling section 120 of the heat exchanger 100.

As illustrated schematically in FIG. 2, the process stream enters the heating section 110 of the heat exchanger 100 at a process stream heating section inlet port 111 p and flows within the heating section 110 along a process stream heating flow path PHFP along (such as alongside, and particularly, such as parallel to) a heating medium flow path HFP. Both paths may be described as extending along a flow path dimension FPD of the heat exchanger 100. A heated or heating or hot (such terms being used interchangeably without intent to limit) medium flows through the heating medium flow path HFP, preferably continuously, to heat the process stream flowing through the heating section 110. The process stream heating flow path PHFP and the heating medium flow path HFP are physically isolated, so that there is no comingling of mediums/fluids therebetween, yet are in thermal communication, so that heat from the heating medium flow path HFP heats the process stream flowing along the process stream heating flow path PHFP.

After reaching the opposite end of the heating section 110, the heated process stream exits the heating section 110 through the process stream heating section outlet port 113 p and is transported to the cooling section 120. In one embodiment, the process stream is transported in a passage or channel (such as though a passage within a mating manifold in fluid communication with the heat exchanger 100, as described in further detail below) transverse to the heating medium flow path HFP, such as along a transfer flow dimension TFD of the heat exchanger 100 transverse to (e.g., perpendicular to) the flow path dimension FPD. This path allows the fluid stream to be held at an elevated temperature for a period of time and is dependent on the volume of the fluid path and flow rate of the process fluid. Generally, for viral inactivation, temperatures must remain elevated for at least about 10 seconds. The process stream enters the cooling section 120 at a process stream cooling section inlet port 121 p and flows within the cooling section 120 along a process stream cooling flow path PCFP along (such as alongside, and particularly, such as parallel to) a cooling medium flow path CFP. Both paths may be described as extending along a flow path dimension FPD of the heat exchanger 100. A cooled or cooling or cold (such terms being used interchangeably without intent to limit) medium flows through the cooling medium flow path CFP to cool the process stream flowing through the cooling section 120. The process stream cooling flow path PCFP and the cooling medium flow path CFP are physically isolated, so that there is no comingling of mediums/fluids therebetween, yet in thermal communication so that the cooling medium flow path CFP cools the process stream flowing along the process stream cooling flow path PCFP. At the end of the process stream cooling flow path PCFP, the process stream is preferably at the desired cooled temperature and exits the heat exchanger 100 through the process stream cooling section outlet port 123 p for collection and/or further processing.

The fluid flow pattern illustrated in FIG. 2 also illustrates examples of fluid flow paths for heating medium and cooling medium in the respective heating section 110 and cooling section 120 of heat exchanger 100. Fluid flow paths are schematically represented in FIG. 2 to illustrate an example of flow paths through the heat exchanger 100 resulting in the desired HTST treatment. However, other configurations are within the scope of the present disclosure. In one embodiment, although the heating medium flow path HFP through the heating section 110 extends along the process stream heating flow path PHFP, the direction of flow of heating medium through the heating medium flow path HFP is in a direction opposite the direction of flow of the process stream through the process stream heating flow path PHFP. In one embodiment, although the cooling medium flow path CFP through the cooling section 120 extends along the process stream cooling flow path PCFP, the direction of flow of cooling medium through the cooling medium flow path CFP is in a direction opposite the direction of flow of the process stream through the process stream cooling flow path PCFP. In one embodiment, the direction of flow of the process stream through the process stream flow path PFP is in a direction opposite the directions of thermal medium flow through both the heating medium flow path HFP and the cooling medium flow path CFP.

More particularly, as illustrated schematically in FIG. 2, in one embodiment, heating medium may enter a heating medium inlet port 111 h at the same side of the heating section 110 as the process stream heating section outlet port 113 p, flow along the heating medium flow path HFP in a direction opposite the direction in which the process stream flows along the process stream heating flow path PHFP, and exit the heating section 110 through a heating section outlet port 113 h at the same side of the heating section 110 as the process stream heating section inlet port 111 p. As such, the temperature of the process stream is increased as it flows from the beginning to the end of the process stream heating flow path PHFP.

Similarly, as illustrated schematically in FIG. 2, cooling medium may enter a cooling medium inlet port 121 c at the same side of the cooling section 120 as the process stream cooling section outlet port 123 p, flow along the cooling medium flow path CFP in a direction opposite the direction in which the process stream flows along the process stream cooling flow path PCFP, and exit the cooling section 120 through a cooling section outlet port 123 c at the same side of the cooling section 120 as the process stream cooling section inlet port 121 p. As such, the temperature of the process stream is decreased as it flows from the beginning to the end of the process stream cooling flow path PCFP until it transitions to the desired final temperature at which it exits the heat exchanger 100.

Various parameters, such as flow rate, heating section 110 and cooling section 120 dimensions, heating medium and cooling medium temperatures, heat exchanger 100 materials, etc., may be chosen to achieve a temperature change in the process stream, within the time frame required for the process stream to enter and exit the heat exchanger 100, sufficient to meet the requirements of HTST treatment to achieve the desired heat inactivation, such as by inactivating any viral components in the process stream.

In the illustrated embodiments, as in known plate and frame heat exchangers, the alternating flow paths within the heat exchanger 100 of the present disclosure are defined by a plurality of flow channels 106 (more particularly, as in the illustrated embodiments, stacks of substantially planar flow channels) through which fluid (process stream or thermal medium) moves. In one embodiment of a heat exchanger 100, the flow channels 106 include a fluid flow channel 107 (through which the process stream or thermal medium flows through the heating section 110 or cooling section 120 of the heat exchanger 100), and thermally conductive physical barriers 108 between the thermal mediums (heating medium or cooling medium) and the process stream. Optionally, a turbulence promoter is provided in the fluid flow channel 107 to optimize heat exchange. The thermally conductive physical barriers 108 physically isolate the thermal mediums (in thermal medium flow channels) from the associated process stream (in adjacent process stream flow channels) while conducting as much heat as possible between the streams to achieve the desired thermal exchange. In some embodiments, at least one heating medium flow path HFP is adjacent a process stream flow path PFP and transfers heat thereto so that the process stream flow paths PFP in the heating section 110 may all be considered process stream heating flow paths PHFP. In some embodiments, heating medium flow paths HFP may alternate with process stream flow path PFP, though other arrangements are within the scope of the present disclosure. Likewise, in some embodiments, at least one cooling medium flow path CFP in the cooling section 120 is adjacent a process stream flow path PFP so that process stream flow paths in the cooling section 120 may all be considered process stream cooling flow paths PCFP. In some embodiments, cooling medium flow paths CFP may alternate with process stream cooling flow paths PCFP, though other arrangements are within the scope of the present disclosure.

In the example of a heat exchanger 100 illustrated in FIGS. 1 and 2, the flow paths within the heating section 110 and the cooling section 120 of the heat exchanger 100 are through fluid flow channels 107 formed or defined by one or more layers of channel spacers 130 stacked together to collectively form the heat exchanger 100. In some embodiments, the channel spacers 130 are formed using adhesives, thermosets, thermoplastics, or compressive forces (as described in further detail below) to form the heat exchanger 100 as a single unit. The channel spacers 130 in each of the heating section 110 and the cooling section 120 form separate flow channels for heating medium, cooling medium, and process stream (such as the flow paths described above) to flow along flow paths through the heating section 110 and the cooling section 120 of the heat exchanger 100. More particularly, in the heating section 110, the channel spacers 130 include heating section channel spacers 130 h defining heating medium flow paths HFP, and process stream channel spacers 130 p forming process stream heating flow paths PHFP, the heating medium flow paths HFP and process stream heating flow paths PHFP being separated (physically isolated) from one another yet thermally coupled by thermally conductive physical barriers 108. Likewise, in the cooling section 120, the channel spacers 130 include cooling section channel spacers 130 c defining cooling medium flow paths CFP, and process stream channel spacers 130 p forming process stream cooling flow paths PCFP, the cooling medium flow paths CFP and process stream cooling flow paths PCFP being separated (physically isolated) from one another, yet thermally coupled by thermally conductive physical barriers 108. The thermally conductive physical barrier 108 between the channel spacers 130 isolates the fluid medium flow paths (thermal medium from process stream) while conducting as much thermal energy as possible between the isolated fluid mediums, as described in further detail below. In some embodiments, a common channel spacer 130 may be provided across the single heat exchanger 100, one part forming fluid flow channels 107 through the heating section 110 and one part forming fluid flow channels 107 through the cooling section 120, the heating and cooling section fluid flow channels 107 being separated by an insulative divider 131 formed therebetween (which, as described in further detail below, may form the insulative wall 104 between the heating section 110 and the cooling section 120). As such, each channel spacer 130 would be formed of a cooling section channel spacer 130 c on one side and a heating section channel spacers 130 h on another side. The various system ports 111 p, 111 h, 113 p, 113 h, 121 p, 121 c, 123 p, and 123 c are formed at the ends of the channel spacers 130 for transport of a given fluid stream (thermal medium or process stream) across the stacked channel spacers 130 (e.g., up or down or vertically along the heat exchanger 100) for distribution of the fluid stream into and out of the channel spacers 130 (e.g., horizontally across the channel spacers 130), as described in greater detail below.

Examples of channel spacers 130 which may be used in the heat exchanger 100 of FIGS. 1 and 2 are shown in isolation in FIGS. 3 and 4. A single channel spacer 130 configured to form a heat exchanger 100 on one side and a cooling section 120 on another side (such that a plurality of channel spacers 130 stacked together form a single heat exchanger 100 comprising, as a unit, a heating section 110 and a cooling section 120) is illustrated, although other configurations are within the scope of the present disclosure. As shown, each channel spacer 130 illustrated in FIG. 3 and FIG. 4 has a flow element 132 and a frame element or seal element 134 (such terms may be used herein interchangeably without intent to limit). In one embodiment, the flow element 132 is a screen (formed of a polymer such as Polypropylene, Polyester, PEEK and fluorinated polymers, or a metal such as stainless steel) creating a tortuous path through which fluid (thermal medium or a process stream) flows. The tortuous path creates turbulence enhancing/facilitating thermal transfer and/or dissipation of heat. In addition, the flow element 132 may be considered to define a stable uniform channel of desired thickness across the fluid flow channel 107. The seal element 134 frames the flow element 132 to retain fluid medium flowing therethrough (at least laterally, the physical barrier 108 isolating fluid mediums from one another along the stack of channel spacers 130). In addition, the seal element 134 may form the peripheral seal 102 about the heat exchanger 100 as a unit (sealing the periphery of the channel spacers 130 and the heat exchanger 100 as a unit to contain all fluid mediums within the heat exchanger 100), and/or the insulative wall 104 separating the heating section 110 and the cooling section 120 within the heat exchanger 100. In one embodiment, the seal element 134 is formed onto (e.g., molded or otherwise saturated on, such as in liquid form, and allowed to solidify on; or bonded such via heat sealing, adhesives, or molding with a thermoplastic or thermoset material) the flow element 132, or a separately formed seal element 134 may be used. The channel spacers 130 may be created and bonded to the surfaces of the physical barriers 108 using adhesives, heat sealing, thermosets, thermoplastics, or compressive force (e.g., from clamps, as described below) to hold or couple the channel spacers 130 together to form the heat exchanger 100 unit.

The process stream flows co-currently through alternate fluid flow channels 107 through the channel spacers 130 in each of the heating section 110 and cooling section 120 with thermal medium flowing co-currently through alternate thermal medium fluid flow channels 107 h, 107 c between the process stream fluid flow channels 107 p. As described above, the thermal mediums may flow counter-currently with respect to the process stream in a given heating/cooling section. In one embodiment, the seal element 134 is a fluid impermeable structure, such as an elastomer (e.g., a polymer such as high density polyethylene or polypropylene, polyurethane, EPDM rubber) or another thermoset or thermoplastic material (e.g., epoxy, silicone, etc.) formed into a barrier to direct a particular fluid medium into a given fluid flow channel 107 and to prevent mixing of adjacent fluid flows so that thermal mediums do not mix with the process stream. Because, as described above, thermal medium fluid flow channels 107 h, 107 c alternate with process stream fluid flow channels 107 p, and different inlet and outlet ports 111 p, 111 h, 113 p, 113 h, 121 p, 121 c, 123 p, and 123 c are provided for or dedicated to different particular fluid flows, the positioning of the seal element 134 with respect to the ports 111 p, 111 h, 113 p, 113 h, 121 p, 121 c, 123 p, and 123 c alternate between adjacent channel spacers 130 to create alternating seals and thus alternating fluid flows through alternating fluid flow channel 107. As such, thermal mediums and process stream are isolated so only the process stream or the thermal medium (and not both) enters a given fluid flow channel 107, as may be appreciated with reference to FIG. 3 in relation to FIG. 4. Specifically, in FIG. 3 the seal element 134 isolates the thermal medium ports 111 h, 113 h, 121 c, and 123 c from the flow element 132, allowing process stream to flow through the process stream ports 111 p, 113 p, 121 p, and 123 p and through the flow element 132. Similarly, in FIG. 4 the seal element 134 isolates the process stream ports 111 p, 113 p, 121 p, and 123 p from the flow element 132, allowing thermal medium to flow through the thermal medium ports 111 h, 113 h, 121 c, and 123 c and the flow element 132.

In order for heat exchanger 100 to effectively heat or cool the process stream, and in order to prevent mixing of fluid mediums between adjacent fluid flow channels 107, physical barriers 108 constructed of heat conductive materials, such as metals (e.g., stainless steel) or heat-conductive polymers (e.g., polymers utilizing heat-conductive additives such as graphite carbon fiber or ceramics such as aluminum nitride and boron nitride), are provided between adjacent channel spacers 130. In one embodiment, as illustrated in FIG. 2, at least one channel spacer 130 for a process stream is provided, surrounded above and below (along the top side and the bottom side) by a physical barrier 108. On the opposite side of each physical barrier 108 (below the physical barrier 108 positioned along the bottom side of the process stream channel spacer 130, and above the physical barrier 108 positioned along the top side of the process stream channel spacer 130) is a channel spacer 130 for thermal medium (e.g., heating medium in the heating section 110, and cooling medium in the cooling section 120) to flow through to perform the desired heat exchange with the process stream. A further physical barrier 108 may be provided on the opposite side of the thermal medium channel spacer 130 if another process channel spacer 130 is to be provided. However, the top and bottom of the heat exchanger 100 need not have physical barriers 108 if a gasket or other sealing element is provided to isolate thermal medium (or another fluid medium) flowing through the channel spacer 130 at the top and/or bottom of the heat exchanger 100, as described in further detail below. As few as three channel spacers 130 (a process stream channel spacer 130 p sandwiched between a pair of heating section channel spacers 130 h or cooling section channel spacers 130 c) may be provided. Such arrangement may be repeated as many times as desired or feasible, depending, e.g., on the scale of the process (as discussed in further detail below). In some embodiments, at least ten, or multiples of ten, or one hundred, or multiples of one 100, or even many as approximately 1000 physical barriers 108 with a channel spacer 130 on either side thereof may be provided.

The physical barriers 108 are formed of a material which prevents fluid flow therethrough, so that when a physical barrier 108 is placed along a channel spacer 130, fluid is retained in that channel spacer 130. In order to allow fluid to be distributed to the fluid flow channels 107 defined by the channel spacers 130 in the heat exchanger 100, the physical barriers 108 between the channel spacers 130 include ports similar to and corresponding with the ports provided in the channel spacers 130 to allow fluid mediums to flow therethrough (e.g., vertically, or perpendicular to the plane of the physical barrier 108) to the channel spacers 130 through which the fluid mediums are to flow (e.g., horizontally or along the plane of the channel spacers 130).

In accordance with one aspect of the present disclosure, a heat exchanger 100 is formed as a disposable and/or single-use device. As may be appreciated by those of ordinary skill in the art, typical considerations for whether a device, such as a device used in a heat exchanger, and particularly such as in sterilization (or at least viral inactivation) processes, is disposable and/or single-use include, without limitation, cost (so that disposability is economically feasible), weight (e.g., readily portable such as manually portable by a single individual without external assistance, i.e., unassisted manual portability), size (so that the size or thickness or bulk of the device does not unduly impede manipulability by a single individual), and other manufacturing considerations (e.g., use of materials which are easier to work with than others, such as easier to form, shape, cut, etc.). Such considerations affect, without limitation, material selection as well as manner of construction. Additionally, it may not be desirable to sterilize and/or reuse a heat exchanger for biotechnology/biopharmaceutical processes in view of various considerations such as cross-contamination and speed (e.g., of productivity as well as process time generally). Thus, generally, it may be desirable for the heat exchanger 100 used in a biotechnology/biopharmaceutical process to be pre-sterilized, e.g., gamma-irradiated, and readily portable (e.g., by a single individual without external assistance). It may be appreciated that use of a polymeric seal element 134 in the channel spacers 130 to isolate flow paths and/or to contain fluid mediums within desired flow channels 106 may also be more cost effective. Selection of materials and/or configurations of physical barriers 108 may also affect whether the heat exchanger 100 may be considered single-use and/or disposable.

Unlike traditional plate and frame heat exchangers, the physical barrier 108 used in at least one embodiment of a heat exchanger 100 formed in accordance with principles of the present disclosure is significantly thinner than the standard stainless steel plates used in traditional plate and frame heat exchangers. More particularly, the thickness of physical barriers 108 used in a disposable heat exchanger 100 may be selected to be several orders of magnitude thinner than plates used in traditional plate and frame heat exchangers so that it is economically feasible for the heat exchanger 100 to be disposable. In some instances, thin elements such as films or foils, are used that are just thick enough to physically isolate thermal mediums (heating or cooling medium) from the process stream and effectively conduct thermal energy, yet not necessarily thick enough to have structural integrity to maintain a wall configuration independently of another support element (such as the housing 101 or even the channel spacers 130). For instance, the physical barriers 108 may have a maximum thickness of approximately 0.010″ (0.254 mm) and as low as approximately 0.001″ (0.025 mm). It will be appreciated that a very thin physical barrier 108 capable of isolating fluid flows may be formed to be readily manipulated and formed, e.g., easier to cut to the desired shape than a steel plate of a traditional plate and frame heat exchanger. A very thin foil or film may not necessarily be thick enough to maintain its own structural stability (e.g., maintain a planar shape) without external support. The flow element 132 and/or seal element 134 of the channel spacers 130 may impart a degree of structural stability to the physical barrier 108 if the physical barrier 108 is too thin to maintain a fixed or at least semi-rigid configuration (e.g., a planar shape) independently. Although it is recognized that considerations for whether a device is disposable (e.g., economic feasibility) is often a relative consideration, those of ordinary skill in the art of heat exchangers will recognize that a heat exchanger using foils or films as physical barriers 108 would be considered disposable when compared to traditional plate and frame heat exchangers.

The heating and cooling mediums may be supplied directly to the heat exchanger 100. In some embodiments, as shown in FIGS. 5 and 6, the heat exchanger 100 is provided in a heat exchanger assembly 200 in which the heating and cooling mediums, and optionally the process stream as well, are first passed through a manifold 202, which collects, moves, and directs the streams to the appropriate ports in the heat exchanger 100. The manifold may be configured to mate with the heat exchanger 100 to consolidate and move fluid from plurality of channels or ports in the heat exchanger 100 to one orifice or port through which the fluid medium is transported from/to a different process or device. Preferably, the manifold 202 facilitates uniform flow of mediums such as by distributing flow substantially evenly across multiple orifices or ports or flow paths. As may be appreciated the manifold contacts the process stream and must be cleaned prior to being re-used or disposed of following use.

As may be appreciated with reference to FIG. 7 in conjunction with FIG. 3, the manifold 202 has a plurality of system inlet and outlet ports 211 p, 211 h, 213 p, 213 h, 221 p, 221 c, 223 p, and 223 c fluidly coupled with corresponding ports 111 p, 111 h, 113 p, 113 h, 121 p, 121 c, 123 p, and 123 c, respectively, of the heat exchanger 100, and plurality of auxiliary or peripheral inlet and outlet ports 201, 203, 215 h, 217 h, 215 c, 217 c fluidly coupled with other devices, equipment, systems, processes, etc., as appropriate. The ports may be best appreciated with reference to an example of a manifold 202 illustrated in FIG. 5, and with reference to the exploded view of FIG. 2 revealing examples of fluid flow paths between the manifold 202 and the heat exchanger 100. It will be appreciated that various connections, locations, shapes, arrangements, etc., of flow paths, channels, ports, etc. other than those shown and described herein are within the scope of the present disclosure, the following description providing only one of a variety of embodiments of principles of the present disclosure with reference to one of various examples. It will be appreciated that other locations and arrangements for the various auxiliary ports 201, 203, 215 h, 217 h, 215 c, 217 c are within the scope of the present disclosure. For example, the illustrated arrangement shows a pair of thermal medium ports with a process stream therebetween, but the reverse arrangement is also within the scope of the present disclosure.

As may be appreciated, the heat exchanger 100 does not heat or cool the heating and cooling mediums on its own. The heating and cooling mediums typically are brought to the desired respective temperatures by separate heating and cooling devices or systems as known in the art, or heretofore developed. In one non-limiting embodiment, the heating medium may be a heated glycol solution heated by a separate heating mechanism. In one non-limiting embodiment which may optionally be used in conjunction with the aforementioned heating embodiment, the cooling medium may be a chilled glycol solution cooled by a separate cooling mechanism. It will be appreciated that other appropriate heating and cooling mediums may be used instead without detracting from principles of the present disclosure and/or use or efficacy of a heat exchanger 100 formed in accordance with one or more principles of the present disclosure.

In the embodiment of FIG. 7, auxiliary or peripheral manifold ports 201, 203, 215 h, 217 h, 215 c, 217 c are provided about the periphery or sides of the manifold 202 to transport fluids to and from the manifold 202 and the heat exchanger assembly 200. For instance, ports 215 h, 217 h, 215 c, 217 c are provided for transport of heating and cooling mediums to and from the heat exchanger 100, such as with the use of a pump (as known in the art or heretofore known, and thus not illustrated). In the example of FIG. 7, a manifold process stream inlet port 201 is provided on one side of manifold 202 substantially in-line with the process stream flow path PFP through the heating section 110 of the heat exchanger 100 (the process stream heating flow path PHFP). As may be appreciated, internal channels within the manifold 202 redirect the process stream upwardly into the heat exchanger 100. A manifold process stream outlet port 203 is provided spaced apart from the manifold process stream inlet port 201 and substantially in-line with the process stream flow path PFP through the cooling section 120 of the heat exchanger 100 (the process stream cooling flow path PCFP). As may be appreciated, internal channels within the manifold 202 redirect the process stream downwardly from the heat exchanger 100 to the manifold process stream outlet port 203.

In the example of FIG. 7, a manifold heating medium inlet port 215 h is provided on another side of manifold 202 (other than the side with the manifold process stream ports 201, 203) to deliver heating medium in a direction substantially transverse to the heating medium flow path HFP through the heating section 110 of the heat exchanger 100. As may be appreciated, internal channels within the manifold 202 redirect the fluid flow upwardly into the heat exchanger 100 and to be in-line with the heating medium flow path HFP. A manifold heating medium outlet port 217 h is provided spaced apart from the manifold heating medium inlet port 215 h enabling similar flow paths as described with respect to the manifold heating medium inlet port 215 h to allow the heating medium to exit the manifold 202 (such as for reheating, and then reentering the manifold 202 via the manifold heating medium inlet port 215 h.

Similarly, in the example of FIG. 7, a manifold cooling medium inlet port 215 c is provided on another side of manifold 202 (other than the side with the manifold process stream ports 201, 203, and opposite the side with the heating medium ports 215 h, 217 h) to deliver cooling medium in a direction substantially transverse to the cooling medium flow path CFP through the cooling section 120 of the heat exchanger 100. As may be appreciated, internal channels within the manifold 202 redirect the fluid flow upwardly into the heat exchanger 100 and to be in-line with the cooling medium flow path CFP. A manifold cooling medium outlet port 217 c is provided spaced apart from the manifold cooling medium inlet port 215 c enabling similar flow paths as described with respect to the manifold cooling medium inlet port 215 c to allow the cooling medium to exit the manifold 202 (such as to be cooled down before reentering the manifold 202 via the manifold cooling medium inlet port 217).

The internal system ports 211 p, 211 h, 213 p, 213 h, 221 p, 221 c, 223 p, 223 c of the manifold 202 are ported in a manner such that various ports of the manifold 202 mate with corresponding ports of the heat exchanger 100, as may be appreciated with referenced to the example of a manifold 202 embodiment illustrated in FIG. 7 in conjunction with the example heat exchanger 100 and fluid flow paths illustrated FIG. 3.

More particularly, a process stream is redirected within the manifold 202 from the manifold process stream inlet port 201 to the manifold heating section process stream feed port 211 p which is in fluid communication with the process stream heating section inlet port 111 p in the heat exchanger 100. The process stream may then flow through the heating section 110 of the heat exchanger 100 as described above. The heated process stream exiting the heating section 110 of the heat exchanger 100 via the process stream heating section outlet port 113 p is then transported back to the manifold 202 via a manifold heating section process stream return port 213 p, transported (e.g., laterally) within the manifold 202 in the direction of the cooling section 120 of the heat exchanger 100 and to the manifold cooling section process stream feed port 221 p which is in fluid communication with the process stream cooling section inlet port 121 p in the heat exchanger 100. The process stream may then flow through the cooling section 120 of the heat exchanger 100 as described above. The cooled process stream exiting the cooling section 120 of the heat exchanger 100 via the process stream cooling section outlet port 123 p is then transported back to the manifold 202 via a manifold cooling section process stream return port 223 p. The process stream may then be transported within the manifold to the manifold process stream outlet port 203 for collection and/or further processing.

In the example of FIG. 7, heating medium entering the manifold 202 through the manifold heating medium inlet port 215 h is directed upwardly and split into at least two (as shown, though additional ports or flow paths are within the scope of the present disclosure) manifold heating section feed ports 211 h which are fluidly coupled with the heating medium inlet port 111 h of the heat exchanger 100. Heating medium may then flow through the heat exchanger 100 as described above. Heating medium exiting the heating section 110 of the heat exchanger 100 via the heating section outlet ports 113 h of the heat exchanger 100 is then transported back to the manifold 202 via heating medium outlet ports 113 h of the manifold 202 fluidly coupled with the heating section outlet ports 113 h of the heat exchanger 100. The heating medium may then exit the heat exchanger assembly 200, such as to be reheated, via the manifold heating medium outlet port 217 h.

Similarly, in the example of FIG. 7, cooling medium entering the manifold 202 through the manifold cooling medium inlet port 215 c is directed upwardly and split into at least two (as shown, though additional ports or flow paths are within the scope of the present disclosure) manifold cooling section feed ports 221 c which are fluidly coupled with the cooling medium inlet port 121 c of the heat exchanger 100. Cooling medium may then flow through the heat exchanger 100 as described above. Cooling medium exiting the cooling section 110 of the heat exchanger 100 via the cooling section outlet ports 123 c of the heat exchanger 100 is then transported back to the manifold 202 via cooling medium outlet ports 123 c of the manifold 202 fluidly coupled with the cooling section outlet ports 123 c of the heat exchanger 100. The cooling medium may then exit the heat exchanger assembly 200, such as to be cooled down, via the manifold cooling medium outlet port 217 c.

It will be appreciated that the path length and flow rate through the heat exchanger 100 and manifold 202 (if used) contribute to the resonance time and mixing rate and may be varied to achieve the desired process stream target temperature and contact time. The heating and cooling rate may be dictated by the capacity of heating medium flow path and the cooling medium flow path. Both temperature and flow rate affect the amount of heat transferred between a given thermal medium and associated process stream.

The heat exchanger assembly 200 of FIGS. 6 and 7 is one possible configuration of a single-use HTST system utilizing a plate and frame design where a manifold 202 and single-use heat exchanger 100 are held together with clamping plates 220, 230, coupled with clamping bolts 240. Such configuration is well known in the art and does not substantially affect the principles of a heat exchanger 100 formed in accordance with the present disclosure and therefore further detail is not necessary for those of ordinary skill in the art to make or use such assembly. It will be appreciated that the clamping plates 210, 220 may contribute forces to holding together channel spacers 130 to form a single unit heat exchanger 100 embodiment as described above. The heat exchanger assembly 200 may be configured such that the clamping plates 220, 230 are non-process stream contact and thus reusable. In one embodiment, the clamping plates 220, 230 may be formed of stainless steel or another rigid material such as aluminum, die cast zinc, carbon fiber, or filled plastic. As may be seen in the exploded view of FIG. 6, a gasket 222, 232 may be provided between a clamping plate 220, 230 and the heat exchanger 100. Each gasket 222, 232 may be formed to create a liquid-tight seal (e.g., create a sealing surface) between the respective top and bottom sides of the heat exchanger 100 and an adjacent component (in the embodiment of FIGS. 5 and 6, the manifold 202 adjacent the bottom of the heat exchanger 100 and the clamping plate 230 adjacent the top of the heat exchanger 100). Examples of materials which may be used to form gaskets 222, 232 include EPDM rubber, silicone-rubber, Buna-N, and polyolefin elastomer. Each gasket may also serve to isolate the process stream from the adjacent, preferably reusable, clamping plate 220, 230. Thus, as noted above, a physical barrier 108 need not be provided at the top or bottom of the heat exchanger 100 as the thermal medium in the channel spacer 130 at the top or bottom is sealed therein with one of the gaskets 222, 232. It will be appreciated that the lower gasket 222 preferably includes ports corresponding to the corresponding ports in the heat exchanger 100 and the manifold 202 so that fluid mediums may flow between the heat exchanger 100 and the manifold 202 through the gasket 222. The gasket 232 adjacent the upper clamping plate 230 and on the side of the heat exchanger 100 not facing/facing away from the manifold 202 preferably does not have any cut-out ports so that the gasket 232 creates a sealing surface between the heat exchanger 100 and the upper clamping plate 230.

It should be appreciated that various embodiments (either individual elements or combinations of elements) illustrated in the figures have several separate and independent features, which each, at least alone, has unique benefits which are desirable for, yet not critical to, the presently disclosed heat exchanger or heat exchanger assembly or method. Therefore, the various separate features described herein need not all be present in order to achieve at least some of the desired characteristics and/or benefits described herein. One or more separate features may be combined, or only one of the various features need be present in a heat exchanger or heat exchanger assembly formed in accordance with various principles of the present disclosure. For instance, it may be desirable simply to heat or cool a process stream without both heating and cooling. It will be appreciated that the disposable/single-use may be independent of the dual-path configuration. Principles of the heat exchanger 100 disclosed herein may be applied for a single-thermal exchange process, e.g., just heating or just cooling.

All apparatuses and methods discussed herein are examples of apparatuses and/or methods implemented in accordance with one or more principles of this disclosure. These examples are not the only way to implement these principles but are merely examples. Thus, references to elements or structures or features in the drawings must be appreciated as references to examples of embodiments of the disclosure, and should not be understood as limiting the disclosure to the specific elements, structures, or features illustrated. Other examples of manners of implementing the disclosed principles will occur to a person of ordinary skill in the art upon reading this disclosure. Although described for use in the context of viral inactivation, the principles of the present disclosure can be applied more broadly if desired. For instance, heat exchanger principles disclosed herein may be applied to continuous heat exchange processes, and/or disposable/single-use heat exchangers, and/or heat exchange processes other than HTST processes.

In the foregoing description and the following claims, the following will be appreciated. The phrases “at least one”, “one or more”, and “and/or”, as used herein, are open-ended expressions that are both conjunctive and disjunctive in operation. The term “a” or “an” or “the” entity, as used herein, refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise. All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, longitudinal, front, back, top, bottom, above, below, vertical, horizontal, radial, axial, clockwise, counterclockwise, and/or the like) are only used for identification purposes to aid the reader's understanding of the present disclosure, and/or serve to distinguish regions of the associated elements from one another, and do not limit the associated element, particularly as to the position, orientation, or use of this disclosure. Connection references (e.g., attached, coupled, connected, and joined) are to be construed broadly and may include intermediate members between a collection of elements and relative movement between elements unless otherwise indicated. As such, connection references do not necessarily infer that two elements are directly connected and in fixed relation to each other. Identification references (e.g., primary, secondary, first, second, third, fourth, etc.) are not intended to connote importance or priority, but are used to distinguish one feature from another.

While the foregoing description and drawings represent various embodiments, it will be understood that various additions, modifications, and substitutions may be made therein without departing from the spirit and scope of the present disclosure. In particular, it will be clear to those skilled in the art that principles of the present disclosure may be embodied in other forms, structures, arrangements, proportions, and with other elements, materials, and components, without departing from the spirit or essential characteristics thereof. One skilled in the art will appreciate that the disclosure may be used with many modifications of structure, arrangement, proportions, materials, and components and otherwise, used in the practice of the disclosure, which are particularly adapted to specific environments and operative requirements without departing from the principles of the present disclosure. For example, elements shown as integrally formed may be constructed of multiple parts or elements shown as multiple parts may be integrally formed, the operation of elements may be reversed or otherwise varied, the size or dimensions of the elements may be varied. The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims, and not limited to the foregoing description.

All of the devices and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the devices and methods of this disclosure have been described in terms of preferred embodiments, it may be apparent to those of skill in the art that variations can be applied to the devices and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the disclosure. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the disclosure as defined by the appended claims. 

What is claimed is:
 1. A heat exchanger comprising: a heating section defining flow paths for heating medium along flow paths for a process stream, the heating medium flow paths physically isolated from and thermally coupled with the process stream flow paths; and a cooling section thermally and physically isolated from said heating section and defining flow paths for cooling medium along flow paths for a process stream, the cooling medium flow paths physically isolated from and thermally coupled with the process stream flow paths; wherein the heat exchanger as a single unit includes process stream ports, heating medium ports, and cooling medium ports.
 2. The heat exchanger of claim 1, further comprising a manifold coupled thereto, said manifold comprising, as a unit, manifold process stream ports corresponding to and in fluid communication with said heat exchanger process stream ports, manifold heating medium ports corresponding to and in fluid communication with said heat exchanger heating medium ports, and manifold cooling medium ports corresponding to and in fluid communication with said heat exchanger cooling medium ports, such that a process stream flows continuously through said heating section to said cooling section through said manifold.
 3. The heat exchanger of claim 2, wherein said manifold receives the process stream that has been heated through said heating section of said heat exchanger, transfers the heated process stream to said cooling section of said heat exchanger, and receives the process stream that has cooled through said cooling section of said heat exchanger.
 4. The heat exchanger of claim 3, wherein said heat exchanger is a single unit and said manifold is a single unit mating with said heat exchanger single unit.
 5. The heat exchanger of claim 1, further comprising a plurality of stacked channel spacers defining said flow paths through said heat exchanger.
 6. The heat exchanger of claim 5, wherein said plurality of channel spacers seal fluid within said heat exchanger and isolate flow paths within said heat exchanger.
 7. The heat exchanger of claim 5, wherein each of said plurality of channel spacers defines said flow paths in said heating section and said cooling section of said heat exchanger.
 8. The heat exchanger of claim 7, wherein each of said plurality of channel spacers comprises a frame element and a flow element, wherein frame elements of stacked channel spacers are bonded together to form a peripheral seal about said heat exchanger as a unit and an insulative wall between said heating section and said cooling section within said heat exchanger.
 9. A heat exchanger comprising: a plurality of channel spacers stacked together, each channel spacer defining a fluid flow channel for a fluid medium to flow therethrough; and a thermally conductive physical barrier, in the form of thin foil or film, sandwiched between adjacent channel spacers to conduct thermal energy between fluid mediums in adjacent channel spacers while physically isolating the fluid mediums from each other.
 10. The heat exchanger of claim 9, wherein said thermally conductive physical barrier is sufficiently thin to allow at least ten thermally conductive physical barrier in said heat exchanger without impeding on unassisted manual portability of said heat exchanger.
 11. The heat exchanger of claim 10, wherein each thermally conductive physical barrier is no greater than 0.010″ thick.
 12. The heat exchanger of claim 9, wherein each thermally conductive physical barrier is in the form of a thin foil or film that cannot maintain structural rigidity and shape unassisted.
 13. The heat exchanger of claim 12, wherein said channel spacers provide structural rigidity to said thermally conductive physical barriers.
 14. The heat exchanger of claim 9, wherein each channel spacer comprises a frame element and a screen element.
 15. The heat exchanger of claim 14, wherein each channel spacer further comprises a seal element sealing fluid flow between the frame element of said channel spacer, an upper thermally conductive physical barrier on one side of said channel spacer, and a lower thermally conductive physical barrier on an opposite side of said channel spacer.
 16. A method of heating and cooling a process stream through a single heat exchanger unit along a continuous flow path using a thermal medium comprising a heating medium or a cooling medium, said method comprising: providing a at least one process stream heating medium flow path and at least one heating medium flow path through a heating section of the single heat exchanger, the heating medium flow path extending along a process stream heating flow path to heat the process stream; and providing a at least one process stream cooling flow path and at least one cooling medium flow path through a cooling section of the single heat exchanger, the cooling medium flow path extending along a process stream cooling flow path to cool the process stream; wherein heating and cooling of a process stream is achieved in the same single heat exchanger.
 17. The method of claim 16, further comprising providing a plurality of system ports in the single heat exchanger, the system ports including process stream ports in fluid communication with the process stream flow paths through the single heat exchanger, and thermal medium ports in fluid communication with heating medium flow paths and cooling medium flow paths in the single heat exchanger.
 18. The method of claim 16, further comprising coupling the single heat exchanger with a mating manifold configured to distribute flow to the system ports in the single heat exchanger.
 19. The method of claim 18, wherein the manifold is provided with inlet and outlet ports for passage of process stream, a heating medium, and a cooling medium into or out of the manifold and thus the single heat exchanger.
 20. The method of claim 16, further comprising coupling the single heat exchanger to a mating manifold, the manifold transferring the process stream from the heating section to the cooling section of the single heat exchanger. 